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RecruitingNCT05856773COMPROUpdated Sep 29, 2026

Conventionally Fractionated vs. Hypofractionated Comprehensive Nodal Irradiation for Breast Cancer Using Pencil Beam Scanning Proton Therapy

A Phase 3 interventional study of Proton Therapy in Breast Cancer, sponsored by Proton Collaborative Group. Recruiting at 9 sites in United States. Open to female participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Proton Collaborative Group · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
276
Allocation
Randomized
Ages
19 Years and older
Sex
Female
01

Study summary

The purpose of this research study is to learn more about the effects of using proton radiation therapy delivered over a shorter course of treatment (3 weeks) compared with a longer, standard course of treatment (5 weeks) for women with breast cancer who require radiotherapy to the breast/chest wall and regional lymph nodes.

Read the detailed description

This study is being done to see if comprehensive regional nodal radiation therapy to the breast or chest wall and regional lymph node area using proton therapy delivered with a hypofractionated approach (less treatment days) will result in rates of treatment related skin and soft tissue side effects that are non-inferior compared to conventionally fractionated proton radiotherapy regimens.

02

Conditions studied

  • Breast Cancer

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Keywords

  • Proton Radiation
03

Who can participate

Ages eligible
19 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with Stage I-III breast cancer who have undergone breast conserving surgery or mastectomy and have been recommended to receive postoperative radiation therapy to the breast or chest wall and regional draining lymph nodes (axilla levels I-III, SCV, IMN)
  • Histologically documented breast cancer (invasive mammary, ductal, medullary, tubular, metaplastic, mucinous, lobular, or ductal carcinoma in situ) for which treatment with radiation therapy to the breast/chest wall and comprehensive regional lymph nodes including the internal mammary chain is recommended
  • No clinical evidence or suspicion of distant metastatic disease
  • History and physical exam within 90 days prior to study registration
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  • Negative pregnancy test for women of child-bearing potential
  • Able to begin radiation treatment within 12 weeks of last surgery or last day of chemotherapy
  • Presence of breast implants, breast expanders, tissue flap, or other breast reconstruction are allowed
  • Bilateral breast cancer is allowed if at least one side will be treated with comprehensive nodal irradiation per protocol treatment and will be recorded as the laterality receiving comprehensive nodal irradiation. If both sides will be treated comprehensively, it will be documented as such

Exclusion criteria

Exclusion Criteria:

  • Presence of skin ulceration and / or ipsilateral satellite nodules and/or edema (including peau d'orange) (T4b or T4c disease) or diagnosis of inflammatory breast cancer (T4d disease)
  • Residual gross disease detected by imaging or clinical exam with the exception of \<2cm internal mammary lymph node or supraclavicular lymph node amenable to sequential boost
  • Prior history of radiation therapy overlapping with current target volume (including intraoperative brachytherapy, interstitial catheter brachytherapy, balloon brachytherapy, external beam radiation therapy)
  • Prior history of explant surgery or implant removal due to infection or wound healing issues without subsequent implant or flap reconstruction
  • Presence of double/dual port tissue expander
  • Clinical or radiographic evidence of distant metastatic disease
  • Pregnant or breast-feeding females
  • Non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
  • History of connective tissue disorder (i.e., systemic lupus erythematosus, scleroderma), dermatomyositis, xeroderma pigmentosum
  • Known BRCA 1 or BRCA 2 mutation
  • Presence of an active skin rash
  • Prior history of breast cancer
  • Prior invasive non-study malignancy unless disease free for ≥ 3 years. Non-melanoma skin cancer, well-differentiated thyroid cancers, in situ carcinomas of the oral cavity, cervix, and other organs, and tumors that are not thought to impact the life expectancy of the patient are permissible.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
276 participants (estimated)

Study arms

  • Active comparator
    Arm A - Standard Fractionation

    50-50.4 Gy (RBE) in 25-28 daily fractions of 1.8-2.0 Gy (RBE) plus a Tumor Bed Boost (for intact breast) of 10 Gy (RBE) in 4-5 daily fractions of 2-2.5 Gy (RBE) \*\*Additional boost of 10-20 Gy (RBE) in 2-2.5 Gy (RBE) fractions to clinically involved lymph nodes or chest wall/scar allowed at the treating physician's discretion\*\*

    Radiation: Proton Therapy

  • Other
    Arm B - Hypofractionation

    40.05 Gy (RBE) in 15 daily fractions of 2.67 Gy (RBE) plus a Tumor Bed Boost (for intact breast) of 10 Gy (RBE) in 4-5 daily fractions of 2-2.5 Gy (RBE) \*\*Additional boost of 10-20 Gy (RBE) in 2-2.5 Gy (RBE) fractions to clinically involved lymph nodes or chest wall/scar allowed at the treating physician's discretion\*\*

    Radiation: Proton Therapy

Interventions

  • RadiationProton Therapy

    Pencil Beam Scanning (PBS)

05

What researchers measure

Primary outcomes

  1. To determine if the rate of grade ≥3 treatment-related skin and soft tissue toxicities with comprehensive nodal irradiation for breast cancer using hypofractionated PBS proton therapy is non-inferior to conventionally-fractionated proton radiotherapy

    This study will investigate if adjuvant comprehensive regional nodal radiotherapy to the breast or chest wall and regional lymph nodes including the axilla (levels I-III), supraclavicular (SCV), and internal mammary (IMN) lymph nodes using pencil beam scanning proton therapy delivered with a hypofractionated regimen results in rates of acute and late grade 3 or worse treatment-related skin and soft tissue toxicities that are non-inferior compared with rates in pencil beam scanning proton therapy using conventionally fractionated regimens.

    Time frame: 2 years after radiation therapy

Secondary outcomes

  1. To determine the rate of any grade ≥3 treatment-related adverse events

    Time frame: 2, 5, and 10 years after radiation therapy

  2. To determine local recurrence rates

    Time frame: 2, 5, and 10 years after radiation therapy

  3. To determine regional recurrence rates

    Time frame: 2, 5, and 10 years after radiation therapy

  4. To determine distant recurrence rates

    Time frame: 2, 5, and 10 years after radiation therapy

  5. To determine breast cancer-specific survival

    Time frame: 2, 5, and 10 years after radiation therapy

  6. To determine overall survival

    Time frame: 2, 5, and 10 years after radiation therapy

  7. To assess patient-reported quality of life

    FACT-B questionnaire

    Time frame: 2, 5, and 10 years after radiation therapy

  8. To assess patient-reported quality of life

    BREAST-Q questionnaire

    Time frame: 2, 5, and 10 years after radiation therapy

  9. To assess physician-reported cosmetic outcomes

    Physician reported cosmesis form

    Time frame: 2, 5, and 10 years after radiation therapy

Other outcomes

  1. To correlate dosimetric parameters with acute and late adverse events for the development of model dose constraints for comprehensive nodal irradiation for breast cancer using a moderately hypofractionated regimen with PBS-PT

    Time frame: 2, 5, and 10 years after radiation therapy

06

Study locations

9 of 9 sites recruiting
  • Mayo Clinic
    Scottsdale, Arizona 85259, United States
    • June Leonard · Contact · leonard.june@mayo.edu · 855-776-0015 (toll free)
    • Carlos Vargas, MD · Principal investigator
    Recruiting
  • California Protons Cancer Therapy Center
    San Diego, California 92121, United States
    Recruiting
  • University of Florida Proton Therapy Institute
    Jacksonville, Florida 32206, United States
    Recruiting
  • Dwoskin Proton Therapy Center
    Miami, Florida 33125, United States
    Recruiting
  • Miami Cancer Institute
    Miami, Florida 33176, United States
    Recruiting
  • Emory Proton Therapy Center
    Atlanta, Georgia 30308, United States
    Recruiting
  • Maryland Proton Treatment Center
    Baltimore, Maryland 21201, United States
    Recruiting
  • New York Proton Center
    New York, New York 10035, United States
    • Ryan Holder · Contact · rholder@nyproton.com · 646-968-9055
    • Isabelle Choi, MD · Principal investigator
    Recruiting
  • Inova Schar Cancer Institute
    Fairfax, Virginia 22031, United States
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT05856773
Lead sponsor
Proton Collaborative Group
Responsible party
Sponsor
First posted
May 12, 2023
Start date
Mar 21, 2024
Primary completion
Feb 2038 (estimated)
Completion
Feb 2041 (estimated)
Last update
Sep 29, 2026

Study contacts

Isabelle Choi, MD
study chair · Proton Collaborative Group

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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